We are interested in the mechanisms by which RNA tumor viruses replicate and induce neoplastic transformation. One of the major issues regarding these events is that concerning the mechanism by which the 70S RNA genome of the virus is converted into provirus DNA by the RNA-directed DNA polymerase. To date evidence regarding the precise nature of proviral DNA synthesis is lacking. Although several models have been proposed to describe these events, very little, if any, supportive data are available. In this grant application we present a novel model of proviral DNA synthesis and preliminary evidence lending support to this model. The studies proposed in this application are directed at establishing the credibility, and rigorously testing the feasibility of this particular model as a possible means of oncornavirus provirus DNA synthesis. This model proposes that circularization of the oncornavirus genome occurs shortly after DNA synthesis is initiated on the primer RNA at the 5' end of the genome. According to the model this process occurs by the removal of the 5' end of the RNA associated with initial DNA transcript by RNase H, followed by the association of the DNA transcript with a complementary sequence at the 3' end of the genome. The model therefore predicts that a specific region of the oncornavirus genome is terminally redundant and the studies proposed in this application are designed to test this prediction. Further studies are proposed to determine the involvement of the location of the primer RNA, RNase H activity and the RNA-directed DNA polymerase in the circularization event. BIBLIOGRAPHIC REFERENCES: Collett, M.S. and Faras, A.J. (1976) DNA polymerase of Rous sarcoma virus: Lack of influence of RNase H on the in vitro transcription of 70S RNA. J. Virol. 17:291-295. Beemon, K., Faras, A.J., Haase, A. and Duesberg, P. (1976) Genomic complexities of murine leukemia and sarcoma reticuloendotheliosis, and visna viruses. J. Virol. 17:525-537.